Our objective is to study the pathogenesis of rabbit coronavirus (RbCV), the rabbit's physiologic response to this virus, and the relatedness of RbCV to other members of the Coronaviridae. Serum neutralization studies against RbCV with antiserum to canine coronavirus (CCV), feline infectious peritonitis (FIP), and transmissible gastroenteritis (TGE) viruses in the intact rabbit were completed. Results were: CCV 2/3, FIP 2/3, TGE 1/3, RbCV 3/3 survived. RbCV alone was lethal. All rabbits receiving RbCV in combination with antiserum to one of the coronaviruses, including RbCV showed clinical signs of disease. As expected RbCV antiserum muted clinical signs the most. RbCV reacted with antisera to CCV, FIP, or TGE produced a typical clinical picture of disease. In some survivors the rectal temperature remained above 40 degrees C for 10-12 days and in others the temperature pattern closely followed that of rabbits receiving RbCV + RbCV antiserum. Gross lesions in those which died were similar to rabbits dying with RbCV alone. Gross lesions were not observed in survivors killed following recovery. Based on previous work showing a 2 way cross with coronavirus 229E (Human), partial cross protection from vaccination with CCV and FIP, and this new data, RbCV is most probably in Group II of the Coronaviridae. Nucleotide homology studies will be required to prove this supposition. Assessment of myocardial damage measuring creatine kinase isozymes are in progress. Further attempts will be made to adapt RbCV to tissue culture. The significance of this work lies in the ability to study a viral disease with a cardiotropism in an animal of sufficient but manageable size to allow sequential clinical and physiological observations. The damage to the rabbit heart by RbCV has a corollary in the human heart with the Coxsackie viruses, Mycoplasma pneumoniae, influenza virus, Herpes zoster, and possibly other infectious agents.